This research program is concerned with the structure, metabolism, and function of protein glycosaminoglycan complexes in normal individuals and individuals with connective tissue disease(s). Emphasis is equally divided between two major subprojects: 1) Anabolism and catabolism for the protein-chondroitin sulfate-keratan sulfate complex: These efforts include studies on the biosynthesis of the repeating disaccharide unit of keratan sulfate and include continued study of a galactosyltransferase and attempts to define how N-acetylglucosamine is incorporated into the repeating disaccharide unit. Catabolic studies are largely concerned with the characterization of two endo-Beta-galactosidases (keratinases) found in species of marine mollusks and the use of these enzymes to elucidate the nature of the structure of the linkage region between the polypeptide core and the repeating disaccharide chain. Studies have been initiated directed at establishing the presence of keratinase(s) in mammalian tissues. 2) Mechanism of "correction" of protein-polysaccharide accumulation in cultured generalized gangliosidosis (GM1) skin fibroblasts: We have established that the carbohydrate portion of a mammalian lysosomal Beta-galactosidase is responsible for the "specific" assimilation of this enzyme by cells. The specific monosaccharide or monosaccharide sequence required for enzyme assimilation and the possible existence of a specific membrane receptor for the enzyme is under investigation. BIBLIOGRAPHIC REFERENCES: Hieber, V., Distler, J., Myerowitz, R., Schmickel, R., and Jourdian, G.W. (1976) The Role of Glycosidically Bound Mannose in the Assimilation of Beta-Galactosidase by Generalized Gangliosidosis Fibroblasts. Biochem. Biophys. Res. Commun. 73, 710. Distler, J.J. and Jourdian, G.W. (1977) The Purification and Properties of an Aryl Beta-Hexosidase from Bovine Liver. Arch. Biochem. Biophys. 178, 631.